Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of tumors, new methods and antitumor chemical compositions are needed. The prevention and control of fungi is also of considerable importance to man, and much research has been devoted to development of antifungal measures.
It has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity of great diversity. Marine life has been the source for the discovery of compounds having varied biological activities. Some of the United States patents which have issued for such inventions are as follows: U.S. Pat. No. 4,548,814 for didemnins, having antiviral activity, were isolated from a marine tunicate; U.S. Pat. No. 4,729,996 discloses compounds, having antitumor properties, that were isolated from marine sponges Teichaxinella morchella and Ptilocaulis walpersi; U.S. Pat. No. 4,808,590 discloses compounds, having antiviral, antitumor, and antifungal properties, isolated from the marine sponge Theonella sp.; and U.S. Pat. No. 4,737,510 discloses compounds, having antiviral and antibacterial properties, isolated from the Caribbean sponge Agelas conifera. Clearly, marine sponges have proved to be a source of biological compounds, and a number of publications have issued disclosing organic compounds derived from marine sponges, including Scheuer, P. J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978-1983, Vol. I-V; Faulkner, D. J., (1984) Natural Products Reports 1:551-598; Natural Products Reports (1986) 3:1-33; Natural Products Reports (1987) 4:539-576; J. Am. Chem. Soc. (1985) 107:4796-4798.
The subject invention concerns novel heterocycle alkaloids. Heterocycle compounds of marine tunicate origin have previously been described in Kobayashi, J., J. Chang, Y. Ohizumi, Y. Hirata, T. Sasaki, T. Ohta and S. Nozoe (1988) Tetrahedron Letters 29:1177-1180. Other heterocycle compounds of marine ascidian origin have been described in Bloor, S., F. J. Schmitz (1987) J. Amer. Chem. Soc. 109:6134; and de Guzman, F. S., F. J. Schmitz (1989) Tetrahedron Letters 30:1069. The present invention, utilizing sponges as a source material has provided the art with a new class of biologically active compounds and new pharmaceutical compositions useful as antitumor and antifungal agents. Subsequent to the filing of our parent application describing the novel compounds and their biological activities claimed here, Schmitz et al. have also reported the isolation of these compounds from marine organisms (Schmitz, F. J., F. S. DeGuzman, M. Bilayet Hossain, D. van der Helm [1991] J. Org. Chem. 56:804-808).
Other advantages and further scope of applicability of the present invention will become apparent from the detailed descriptions given herein; it should be understood, however, that the detailed descriptions, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent from such descriptions.